Roche steers Gazyva into a new PhIII program after combo shows promise in lupus nephritis study
Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.
The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.
The drug, which is being tested alone and in combination with other therapies across a range of blood cancers, is engineered to attach to CD20, a protein found on certain B-cells. It is thought to work by attacking targeted cells both directly and in tandem with the body’s immune system. Gazyva, which is already approved for use in certain cancers, generated nearly $342 million in the first nine months of 2019 and has been granted breakthrough therapy status for lupus nephritis.
On the safety side, worries that profound B cell depletion would hamper the drug’s profile were abated after the Gazyva arm registered a serious adverse event rate of 24%, while patients on the standard care arm saw a rate of 29%. In terms of serious infections, the rate was 9% on the Gazyva arm and 18% in the standard group.
“The strategy to target B cells (antibody-producing white blood cells responsible for producing lupus antibodies) in systemic lupus and lupus nephritis was biologically sound. However, two studies did not achieve their respective endpoints,” said Richard Furie, chief of rheumatology at Northwell Health in a statement.
“After a hiatus of several years, a decision was made to move forward with a third-generation B cell-depleting antibody…The hypothesis was that a more potent antibody might result in greater depletion of B cells and that this may yield a greater clinical response in those patients with active kidney disease.”
Lupus is a drug developer’s nightmare. In the last six decades, there has been one FDA approval. In recent years, the field has resembled a graveyard. Last October, UCB and Biogen’s $BIIB anti-CD40L drug failed in a late-stage study, months after Xencor $XNCR and Sanofi’s $SNY Ablynx also conceded defeat in their programs. In August, however, AstraZeneca offered a glimmer of hope after its drug, anifrolumab, cleared a Phase III study.
The only biologic so far to win approval for lupus is GSK’s $GSK Benlysta — which was cleared for adult use in 2011 and for rare cases of childhood lupus this year. (GSK is in the midst of testing Benlysta in combination with Roche’s rituximab in the hope the combination will have a more potent effect on the disease versus Benlysta monotherapy.)
The systemic autoimmune disease, in which the body’s immune system launches an attack on its own tissues and organs, affects about 1.5 million Americans, according to The Lupus Foundation of America. Lupus nephritis occurs when the disease ravages the kidneys, triggering inflammation that could lead to blood and/or protein in the urine, high blood pressure, poor kidney function, or kidney failure. Roughly 60% of lupus patients develop lupus nephritis and 1 in 4 progress to end-stage renal disease.
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